This is a randomized controlled study of Thymitaq, a thymidylate synthase inhibitor, which is given as a continuous infusion versus methotrexate in patients with advanced head and neck cancer who have failed first-line therapy. The primary objective is to compare rate of response to treatment between the two regimens. Secondary objectives include duration of response, duration of progression free survival and duration of overall survival. Toxicities and quality of life issues will also be assessed.